The research proposed in this renewal application is concerned with the possible factors regulating the production of ribosomes in mammalian cells. Recent experiments have suggested that the supply of ribosomal protein is one of these regulatory factors and may be determined by the rate of transport of these proteins from their synthesis site in the cytoplasm to their site of utilization in the nucleolus. Because ribosomal proteins are basic and tend to aggregate under physiological conditions, it seems likely that enzymatic modifications such as phosphorylation and acetylation may be important in the transport process. This may also be true for histones. To test this idea and to further study some of the features of the synthesis and utilization of these proteins, mouse L-cells (a permanent tissue culture line) will be labeled with the radioactive precursors of these modifying groups. Appropriately modified proteins will be isolated from the various subcellular fractions and analyzed for the presence of nascent ribosomal proteins and histones. The kinetics of transport of these proteins will be studied, as will be the environmental and intracellular factors influencing it. The results of these experiments should be important in increasing our understanding of the mechanisms regulating the growth and division of cells, since cellular growth is ultimately determined in part by the abundance and rate of production of ribsomes - the particles on which all protein synthesis takes place.